Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome

We report the isolation of the 5′ flanking region of GRAF (GTPase regulator associated with the focal adhesion kinase), previously described as a putative tumour suppressor gene of acute myelogenous leukaemia and myelodysplastic syndrome, and demonstrate its promoter activity in reporter gene assays...

Descripción completa

Detalles Bibliográficos
Autores principales: Bojesen, S E, Ammerpohl, O, Weinhäusl, A, Haas, O A, Mettal, H, Bohle, R M, Borkhardt, A, Fuchs, U
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2006
Materias:
Genetics and Genomics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361128/
https://www.ncbi.nlm.nih.gov/pubmed/16404424
http://dx.doi.org/10.1038/sj.bjc.6602939
_version_ 1782153146339950592
author Bojesen, S E
Ammerpohl, O
Weinhäusl, A
Haas, O A
Mettal, H
Bohle, R M
Borkhardt, A
Fuchs, U
author_facet Bojesen, S E
Ammerpohl, O
Weinhäusl, A
Haas, O A
Mettal, H
Bohle, R M
Borkhardt, A
Fuchs, U
author_sort Bojesen, S E
collection PubMed
description We report the isolation of the 5′ flanking region of GRAF (GTPase regulator associated with the focal adhesion kinase), previously described as a putative tumour suppressor gene of acute myelogenous leukaemia and myelodysplastic syndrome, and demonstrate its promoter activity in reporter gene assays. Two putative protein-binding sites are identified of which one was sensitive to CpG methylation. The suppressed GRAF expression could be restored in leukaemia cell lines by treatment with a demethylating agent and an inhibitor of histone deacetylases. In contrast to normal tissues, which tested negative for GRAF promoter methylation, 11 of 29 (38%) bone marrow samples from patients with acute myeloid leukaemia or myelodysplastic syndrome were positive.
format Text
id pubmed-2361128
institution National Center for Biotechnology Information
language English
publishDate 2006
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-23611282009-09-10 Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome Bojesen, S E Ammerpohl, O Weinhäusl, A Haas, O A Mettal, H Bohle, R M Borkhardt, A Fuchs, U Br J Cancer Genetics and Genomics We report the isolation of the 5′ flanking region of GRAF (GTPase regulator associated with the focal adhesion kinase), previously described as a putative tumour suppressor gene of acute myelogenous leukaemia and myelodysplastic syndrome, and demonstrate its promoter activity in reporter gene assays. Two putative protein-binding sites are identified of which one was sensitive to CpG methylation. The suppressed GRAF expression could be restored in leukaemia cell lines by treatment with a demethylating agent and an inhibitor of histone deacetylases. In contrast to normal tissues, which tested negative for GRAF promoter methylation, 11 of 29 (38%) bone marrow samples from patients with acute myeloid leukaemia or myelodysplastic syndrome were positive. Nature Publishing Group 2006-01-30 2006-01-10 /pmc/articles/PMC2361128/ /pubmed/16404424 http://dx.doi.org/10.1038/sj.bjc.6602939 Text en Copyright © 2006 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Genetics and Genomics
Bojesen, S E
Ammerpohl, O
Weinhäusl, A
Haas, O A
Mettal, H
Bohle, R M
Borkhardt, A
Fuchs, U
Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome
title Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome
title_full Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome
title_fullStr Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome
title_full_unstemmed Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome
title_short Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome
title_sort characterisation of the graf gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361128/
https://www.ncbi.nlm.nih.gov/pubmed/16404424
http://dx.doi.org/10.1038/sj.bjc.6602939
work_keys_str_mv AT bojesense characterisationofthegrafgenepromoteranditsmethylationinpatientswithacutemyeloidleukaemiaandmyelodysplasticsyndrome
AT ammerpohlo characterisationofthegrafgenepromoteranditsmethylationinpatientswithacutemyeloidleukaemiaandmyelodysplasticsyndrome
AT weinhausla characterisationofthegrafgenepromoteranditsmethylationinpatientswithacutemyeloidleukaemiaandmyelodysplasticsyndrome
AT haasoa characterisationofthegrafgenepromoteranditsmethylationinpatientswithacutemyeloidleukaemiaandmyelodysplasticsyndrome
AT mettalh characterisationofthegrafgenepromoteranditsmethylationinpatientswithacutemyeloidleukaemiaandmyelodysplasticsyndrome
AT bohlerm characterisationofthegrafgenepromoteranditsmethylationinpatientswithacutemyeloidleukaemiaandmyelodysplasticsyndrome
AT borkhardta characterisationofthegrafgenepromoteranditsmethylationinpatientswithacutemyeloidleukaemiaandmyelodysplasticsyndrome
AT fuchsu characterisationofthegrafgenepromoteranditsmethylationinpatientswithacutemyeloidleukaemiaandmyelodysplasticsyndrome

Ejemplares similares